Trends in Non-Tuberculous Mycobacterial Lung Disease and Treatment Outcomes in a Low-Tuberculosis Prevalence Setting: A Retrospective Analysis.

BACKGROUND: Information on the management of non-tuberculous mycobacterial (NTM) lung infection and disease is scarce. The aim of this study was to investigate the trends in NTM lung infections, and the factors associated with the initiation of treatment and treatment outcomes. METHODS: A retrospective analysis was carried out on patient medical records from Haukeland University Hospital, Bergen, Norway, from 2000 to 2021. RESULTS: Among 154 patients with NTM lung infection, the majority (70%) were older than 65 years, and 49% had an underlying pulmonary comorbidity. The most frequently observed mycobacterial species was M. avium complex (MAC), followed by M. malmoense and M. abscessus. In total, 72 (47%) patients received antibiotic treatment. Patients with high symptom scores, aged below 65, and with MAC infection had more than three times the odds of receiving antibiotic treatment. A favourable response and culture conversion was observed in 53 of 72 (74%) patients. However, 17 (32%) of them had a relapse. Out of 82 patients who did not receive treatment, 45 (55%) had spontaneous culture conversion, and 8 (18%) of them had a relapse. No factor was identified to be significantly associated with a favourable treatment response. CONCLUSION: A favourable response to treatment was seen in 74% of patients with a high relapse rate.

The airway microbiota and exacerbations of COPD.

AIM: The aim of this study was to investigate whether the compositionality of the lower airway microbiota predicts later exacerbation risk in persons with COPD in a cohort study. MATERIALS AND METHODS: We collected lower airways microbiota samples by bronchoalveolar lavage and protected specimen brushes, and oral wash samples from 122 participants with COPD. Bacterial DNA was extracted from all samples, before we sequenced the V3-V4 region of the 16S RNA gene. The frequency of moderate and severe COPD exacerbations was surveyed in telephone interviews and in a follow-up visit. Compositional taxonomy and α and ß diversity were compared between participants with and without later exacerbations. RESULTS: The four most abundant phyla were Firmicutes, Bacteroidetes, Proteobacteria and Fusobacteria in both groups, and the four most abundant genera were Streptococcus, Veillonella, Prevotella and Gemella. The relative abundances of different taxa showed a large variation between samples and individuals, and no statistically significant difference of either compositional taxonomy, or α or ß diversity could be found between participants with and without COPD exacerbations within follow-up. CONCLUSION: The findings from the current study indicate that individual differences in the lower airway microbiota in persons with COPD far outweigh group differences between frequent and nonfrequent COPD exacerbators, and that the compositionality of the microbiota is so complex as to present large challenges for use as a biomarker of later exacerbations.

Complications and discomfort after research bronchoscopy in the MicroCOPD study.

BACKGROUND: Data on discomfort and complications from research bronchoscopy in chronic obstructive pulmonary disease (COPD) and asthma is limited. We present complications and discomfort occurring within a week after bronchoscopy, and investigate personal and procedural risk factors. METHODS: 239 subjects with COPD, asthma or without lung disease underwent research bronchoscopies as part of a microbiome study of the lower airways (the MicroCOPD study). Bronchoscopy was done in the supine position with oral scope insertion with the option of light conscious alfentanil sedation. Sampling consisted of protected specimen brushes, bronchoalveolar lavage, small volume lavage and for some, endobronchial biopsies. Bleeding, desaturation, cough, haemodynamic changes, dyspnoea and other events that required an unplanned intervention or early termination of bronchoscopy were prospectively recorded. Follow-up consisted of a telephone interview where subjects rated discomfort and answered questions about fever sensation and respiratory symptoms in the week following bronchoscopy. RESULTS: An unplanned intervention or early termination of bronchoscopy was required in 25.9% of bronchoscopies. Three subjects (1.3%) experienced potentially severe complications, of which all recovered without sequelae. COPD subjects experienced more dyspnoea than controls. Sedation and lower age was associated with less unplanned intervention or premature termination. About half of the subjects (47.7%) reported fever. Discomfort was associated with postprocedural fever, dread of bronchoscopy, higher score on the COPD Assessment Test and never-smoking. In subjects undergoing more than one bronchoscopy, the first bronchoscopy was often predictive for complications and postprocedural fever in the repeated bronchoscopy. CONCLUSION: Research bronchoscopies were not associated with more complications or discomfort in COPD subjects. 47.7% experienced postbronchoscopy fever sensation, which was associated with discomfort.

Complications and discomfort of bronchoscopy: a systematic review.

OBJECTIVE: To identify bronchoscopy-related complications and discomfort, meaningful complication rates, and predictors. METHOD: We conducted a systematic literature search in PubMed on 8 February 2016, using a search strategy including the PICO model, on complications and discomfort related to bronchoscopy and related sampling techniques. RESULTS: The search yielded 1,707 hits, of which 45 publications were eligible for full review. Rates of mortality and severe complications were low. Other complications, for instance, hypoxaemia, bleeding, pneumothorax, and fever, were usually not related to patient characteristics or aspects of the procedure, and complication rates showed considerable ranges. Measures of patient discomfort differed considerably, and results were difficult to compare between different study populations. CONCLUSION: More research on safety aspects of bronchoscopy is needed to conclude on complication rates and patient- and procedure-related predictors of complications and discomfort.

Participation in research bronchoscopy: a literature review.

Bronchoscopy is the preferred method for collecting biological samples from the lower airways of subjects in clinical research. However, ensuring participation in clinical research can be challenging when the research includes an invasive procedure. For this report we reviewed the literature to look for information on participation in research bronchoscopy studies to better design our own study, the Bergen COPD Microbiome study (MicroCOPD). We performed a systematic literature search on participation in research bronchoscopy studies in February 2014 using the search engines of PubMed and EMBASE. The literature search resulted in seven relevant papers. Motivation was an end point in six of the seven papers, but reasons for declining participation and recruitment strategies also seemed important. Human subjects participate in research bronchoscopy studies for personal benefit and altruistic reasons. Inconvenience associated with research, in addition to fear of procedures, is considered a barrier. Radio, especially news stations, generated the most inquiries for a clinical study involving bronchoscopy. There is a lack of information on participation in research bronchoscopy studies in the literature. A bronchoscopy study has been initiated at Haukeland University Hospital, Bergen, Norway, to examine the role of the microbiome in COPD, and participation will be explored as a substudy.

Reference values for within-breath pulmonary impedance parameters in asymptomatic elderly.

INTRODUCTION: A new application for the forced oscillation technique (FOT) has been described by Dellaca et al. using sinusoidal pressure variations at 5 Hz to detect expiratory flow limitation by measuring the within-breath reactance [termed difference between inspiratory and expiratory X5 (DX5)]. Few studies have been performed on respiratory phase differences in the elderly. OBJECTIVE: Our aim was to present reference values for within-breath impedance measurements and to examine how the earlier mentioned method performs in a study population of asymptomatic elderly. METHODS: An age- and sex-stratified random sample was drawn from the elderly population of Bergen, Norway. Among the healthy non-smoking responders from a postal questionnaire study, 148 were selected to perform FOT measurements using an impulse oscillometry system (IOS). Seventy five of these participants had a normal spirometry and were able to perform at least two valid FOT measurements. Predictive equations for men and women were created for FOT parameters by linear multiple regression analysis. DX5 was calculated from the within-breath variation of reactance at 5 Hz. RESULTS/CONCLUSION: This study presents reference values for whole-breath and within-breath impedance parameters in asymptomatic elderly aged >70 years using the IOS method. We found higher resistance measurements than what is reported in previous studies and significantly larger frequency dependence.

Chronic obstructive pulmonary disease is associated with low levels of vitamin D.

INTRODUCTION: COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported. METHODS: Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40-76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls. Levels <20 ng/mL defined deficiency. Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO(2)), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models. RESULTS: COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI. Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = -6.63), current smoking ( = -4.02), GOLD stage III- IV ( = -4.71, = -5.64), and depression ( = -3.29). Summertime decreased the risk of vitamin D deficiency (OR = 0.22). CONCLUSION: COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels.

Explained variance for blood gases in a population with COPD.

INTRODUCTION: Variation of blood gas levels in chronic obstructive pulmonary disease (COPD) patients has not been extensively reported and there is limited knowledge about predictors of chronic respiratory failure in COPD patients. OBJECTIVES: The aim of this study was to identify predictors of hypoxemia, hypercapnia and increased alveolar-arterial oxygen difference in COPD patients. We hypothesized that prediction of arterial blood gases will be improved in multivariate models including measurements of lung function, anthropometry and systemic inflammation. METHODS: A cross-sectional sample of 382 Norwegian COPD patients, age 40-76, Global Initiative for Chronic Obstructive Lung Disease stage II-IV, with a smoking history of at least 10 pack-years, underwent extensive measurements, including medical examination, arterial blood gases, systemic inflammatory markers, spirometry, plethysmography, respiratory impedance and bioelectrical impedance. Possible predictors of arterial oxygen (PaO(2)), arterial carbon dioxide (PaCO(2)) and alveolar-arterial oxygen difference (AaO(2)) were analyzed with both bivariate and multiple regression methods. RESULTS: We found that various lung function measurements were significantly associated with PaO2, PaCO(2) and AaO(2). In addition, heart rate and Fat Mass Index were predictors of PaO(2) and AaO(2), while heart failure and current smoking status were associated with PaCO(2). The explained variance (R(2)) in the final multivariate regression models was 0.14-0.20. CONCLUSIONS: With a wide assortment of possible clinical predictors, we could explain 14-20% of the variation in blood gas measurements in COPD patients.

Cost minimization analysis for combinations of sampling techniques in bronchoscopy of endobronchial lesions.

BACKGROUND: The choice of sampling techniques in bronchoscopy with sampling from a visible lesion will depend on the expected diagnostic yields and the costs of the sampling techniques. AIMS: The aim of this study was to determine the most economical combination of sampling techniques when approaching endobronchial visible lesions. METHODS: A cost minimization analysis was performed. All bronchoscopies from 2003 and 2004 at Haukeland university hospital, Bergen, Norway, were reviewed retrospectively for diagnostic yields. 162 patients with endobronchial disease were included. Potential sampling techniques used were biopsy, brushing, endobronchial needle aspiration (EBNA) and washings. Costs were estimated based on registration of equipment costs and personnel costs. Sensitivity analyses were performed to determine threshold values. RESULTS: The combination of biopsy, brushing and EBNA was the most economical strategy with an average cost of Euro 893 (95% CI: 657, 1336). The cost of brushing had to be below Euro 83 and it had to increase the diagnostic yield more than 2.2%, for biopsy and brushing to be more economical than biopsy alone. The combination of biopsy, brushing and EBNA was more economical than biopsy and brushing when the cost of EBNA was below Euro 205 and the increase in diagnostic yield was above 5.2%. CONCLUSION: In the current study setting, biopsy, brushing and EBNA was the most economical combination of sampling techniques for endobronchial visible lesions.